FARMAKOLOGIFARMAKOLOGI

BEBAN STUDI = 3 SKS BEBAN STUDI = 3 SKS Kuliah = 2 SKS dan Praktikum = 1 SKSKuliah = 2 SKS dan Praktikum = 1 SKSDosen Pengasuh : 5 OrangDosen Pengasuh : 5 OrangGBPP GBPP SAP yang telah disepakati terdiri dari :SAP yang telah disepakati terdiri dari :1. Farmakologi Umum (4 jam)1. Farmakologi Umum (4 jam)2. Obat ANS & Relaksasi otot (6 jam)2. Obat ANS & Relaksasi otot (6 jam)

3. Obat Anestesi lokal & umum (4 jam)3. Obat Anestesi lokal & umum (4 jam)4. Obat Diuretik (2 jam)4. Obat Diuretik (2 jam)5. Obat Sedatif-Hipnotik & CNS Stimulan (2 5. Obat Sedatif-Hipnotik & CNS Stimulan (2 jam)jam)6. Obat Analgesik, antipiretik & antiinflamasi 6. Obat Analgesik, antipiretik & antiinflamasi (2 jam)(2 jam)7. Obat Hemostatika (2 jam)7. Obat Hemostatika (2 jam)8. Hormon & Uterotonika (2 jam)8. Hormon & Uterotonika (2 jam)9. Histamin dan Antihistamin (2 jam)9. Histamin dan Antihistamin (2 jam)

Pembobotan Penilaian Mata Pembobotan Penilaian Mata Kuliah :Kuliah :1. Tugas1. Tugas : bobot 1,5 = 13,64%: bobot 1,5 = 13,64%2. Kuis/tentamen dll : bobot 1,5 = 13,64%2. Kuis/tentamen dll : bobot 1,5 = 13,64%3. Soft skill3. Soft skill : bobot 1 = 9,09% : bobot 1 = 9,09%4. UTS4. UTS : bobot 2 = 18,8% : bobot 2 = 18,8%5. UAS5. UAS : bobot 3 : bobot 3 = 27,27% = 27,27%6. Praktikum6. Praktikum : bobot 2 : bobot 2 = 18.18% = 18.18%

bobot 11 = 100%bobot 11 = 100%

Presensi : Wajib kuliah :Presensi : Wajib kuliah :Nilai E minimal 75%Nilai E minimal 75%Nilai D,C & BC minimal 50%Nilai D,C & BC minimal 50%

PRAKTIKUM (1 SKS)PRAKTIKUM (1 SKS)GBPP GBPP SAP disepakati 6 materi praktikum : SAP disepakati 6 materi praktikum :

1. Cara pemberian obat1. Cara pemberian obat2. Obat yg berpengaruh thd. Tekanan darah2. Obat yg berpengaruh thd. Tekanan darah3. Mengenal stadium anestesi umum3. Mengenal stadium anestesi umum4. Obat yg berpengaruh pada Diuresis4. Obat yg berpengaruh pada Diuresis5. Obat menurunkan rasa nyeri5. Obat menurunkan rasa nyeri6. Obat penghambat inflamasi.6. Obat penghambat inflamasi.

Presensi : Wajib Praktikum 100%Presensi : Wajib Praktikum 100%Kelompok Praktikum Kelompok Praktikum Dibagi 6 kelompok : Dibagi 6 kelompok :

A1 dari kelas A nomor urut 1-45A1 dari kelas A nomor urut 1-45A2 dari kelas A nomor urut 46-69A2 dari kelas A nomor urut 46-69B1 dari kelas B nomor urut 1-55B1 dari kelas B nomor urut 1-55B2 dari kelas B nomor urut 56-70B2 dari kelas B nomor urut 56-70 C dari kelas C ; dan C dari kelas C ; dan

D dari kelas DD dari kelas D

BY :BY :

D.K. MelesD.K. Meles

PHARMACOLOGYPHARMACOLOGY

PHARMACON = Drug/ PoisonPHARMACON = Drug/ PoisonLOGOS = ScienceLOGOS = Science

PHARMACOLOGY : Science to Study of drugPHARMACOLOGY : Science to Study of drugDRUG : All of substance to influence life system DRUG : All of substance to influence life system

application to prevent, diagnostic application to prevent, diagnostic and therapeuticsand therapeutics

SCOPE OF PHARMACOLOGY -SCOPE OF PHARMACOLOGY -PHARMACOKINETICPHARMACOKINETICPHARMACODYNAMICPHARMACODYNAMICPHARMACOTHERAPEUTICPHARMACOTHERAPEUTICPHARMACOGNOSIPHARMACOGNOSITOXICOLOGYTOXICOLOGY

DRUG DRUG All of Substance to influence All of Substance to influence life process in use to prevent, life process in use to prevent, therapeutics and diagnostic of therapeutics and diagnostic of disease.disease.

Have criterion :Have criterion :

1. Effectiveness & Rivesible effect1. Effectiveness & Rivesible effect

2. Savety (Margin of savety) 2. Savety (Margin of savety) Therapeutics Index.Therapeutics Index.

3. High Selectivity3. High Selectivity

PHARMACOKINETICPHARMACOKINETIC ABSORPTION ABSORPTION DISTRIBUTIONDISTRIBUTION BIOTRANSFORMATIONBIOTRANSFORMATION EXCRETIONEXCRETION

ABSORPSI OBAT : ABSORPSI OBAT : Moving Process or Moving Process or to remove of drug from tissue to to remove of drug from tissue to another tissue another tissue to cross the to cross the membrane with spesific mechanism.membrane with spesific mechanism.

1.1. TRANSPORT PASIVETRANSPORT PASIVE Different Different Concentration, No need Energy, non Concentration, No need Energy, non spesificspesificDIFFUSIONDIFFUSION NON-IONIC NON-IONICFILTRATION FILTRATION POROUS POROUSFASCILITATIVE DIFFUSION FASCILITATIVE DIFFUSION CARRIER CARRIER

2.2. TRANSPORT ACTIVETRANSPORT ACTIVE OPPOSITION OPPOSITION GRADIENS CONCENTRATION, Need GRADIENS CONCENTRATION, Need Energy & Spesificity Energy & Spesificity

3. 3. PINOSITOSIS/ EXOSITOSIS/ ENDOSITOSIS.PINOSITOSIS/ EXOSITOSIS/ ENDOSITOSIS.

DRUG ABSORBTION DRUG ABSORBTION Account in % from Account in % from drug dosedrug dose

DRUG BIOAVAILABILITYDRUG BIOAVAILABILITY Prosentage drug Prosentage drug to reach site of action. Was count from dose to reach site of action. Was count from dose of drug (for drug sistemik only).of drug (for drug sistemik only).

FACTOR2 TO INFLUENCE RATE OF DRUG FACTOR2 TO INFLUENCE RATE OF DRUG ABSORBTION :ABSORBTION :1. Route of drug application1. Route of drug application2. Circulation of place application drug.2. Circulation of place application drug.3. Solubelity of drug3. Solubelity of drug4. Ionization Rate of Drug4. Ionization Rate of Drug5. Broad of absorbtion area.5. Broad of absorbtion area.6. Size of molecule particle of drug6. Size of molecule particle of drug7. Drug Formulation7. Drug Formulation

ROUTE OF DRUG ADMINISTRATIONROUTE OF DRUG ADMINISTRATION1. ENTERAL (SUBLINGUAL, PER-ORAL, PER-ANAL)1. ENTERAL (SUBLINGUAL, PER-ORAL, PER-ANAL)

2. PARENTERAL (SC., IM., IV., INTRAPERITONEAL)2. PARENTERAL (SC., IM., IV., INTRAPERITONEAL)

3. TOPICAL (SKIN, MUCOSA)3. TOPICAL (SKIN, MUCOSA)

4. PERINHALATION.4. PERINHALATION.

Sub-Lingual :Sub-Lingual :ConditionCondition : : Iritation, Damage by Iritation, Damage by

gastric Acidgastric Acid

&Damage from drug metabolis.To clause &Damage from drug metabolis.To clause

Dilute in saliva, Non-iritan & Lipofilik.Dilute in saliva, Non-iritan & Lipofilik.

PER-ORAL :PER-ORAL : General, easy, safety and cheap.General, easy, safety and cheap. Influenced by GIT motilityInfluenced by GIT motility Absorbtion Absorbtion Diffusi pasive, depend on Diffusi pasive, depend on

rate of disolution & disintegration.rate of disolution & disintegration. No application in consciousless. No application in consciousless.

PER-RECTUMPER-RECTUM Applicated in condition : gastric Applicated in condition : gastric

iritation, vomiting, damage by gastric iritation, vomiting, damage by gastric acid.acid.

Rate of absorbtion irreguler, Rate of absorbtion irreguler, Sometimes rectum irritationSometimes rectum irritation

Per-injection :Per-injection :

Benefid : Quick in absorbtion, vomit Benefid : Quick in absorbtion, vomit condition consciousless and emergency condition consciousless and emergency applicatedapplicated

Wickedness : must be sterilzation, can”t Wickedness : must be sterilzation, can”t self self uses, pain, & uses, pain, & ralative more ralative more expensive.expensive.

Intra-Vena :Intra-Vena : No absorbtion process No absorbtion process direct in blood direct in blood Onset dan Duration Onset dan Duration quickly quickly Iritatif drug can applicatedIritatif drug can applicated Drug toxicity Drug toxicity Low in therapeutics Index Low in therapeutics Index Must be carefullyMust be carefully

Intra-muskuler (I.M.) dan Sub-kutan (S.C.)Intra-muskuler (I.M.) dan Sub-kutan (S.C.)

Condition : non-iritan drug, water soluble or Condition : non-iritan drug, water soluble or suspention form. suspention form.

Quick in effect (im=Sc).Quick in effect (im=Sc).

Intraperitoneal :Intraperitoneal :In animal experimental applicated onlyIn animal experimental applicated only opten opten

infection.infection.Subtitute i.v. routeSubtitute i.v. route

Per-inhalation : Per-inhalation : Use in gas form drug.Use in gas form drug. Absorbtion a cross epithel mucosa & quick. Absorbtion a cross epithel mucosa & quick. Need tools/ specific methodeNeed tools/ specific methode Dificult in dose countDificult in dose count Topical Topical Unguentum, drops for mocosa & skin Unguentum, drops for mocosa & skin

DRUG DISTRBUTIONDRUG DISTRBUTION

AFTER ABSORBTION AFTER ABSORBTION

Extracelluler Fluids (Extracelluler Fluids (Plasma Plasma ++ 4%,Interstesiil 4%,Interstesiil ++ 13%). 13%).DRUG DRUG Protein plasma bound, Inactivation/ Protein plasma bound, Inactivation/

metabolism process, metabolism process, Bound in reseptorBound in reseptor Respon/ drug Respon/ drug

effect, effect, Exretion Exretion Renal Renal

Intraseluler Fluid Intraseluler Fluid ++ 41% 41%DRUGDRUG Reseptor Reseptor drug respons drug respons

Prot. tissue. Prot. tissue. Non Spesific & Non Spesific & Reversibel.Reversibel. Bound in Fat Bound in Fat Drug Reservoir. Drug Reservoir.

Metabolism (Biotransformation).Metabolism (Biotransformation).

Drugs lipid solubleDrugs lipid soluble easy a cross membrane and easy a cross membrane and distribution to intracelluler fluids, distribution to intracelluler fluids, distribusi ke intraseluler. distribusi ke intraseluler.

Opposite on non lipid soluble drugOpposite on non lipid soluble drug

BIOTRANSFORMATION:BIOTRANSFORMATION:

MECHANISME TO CHANGE DRUGS MECHANISME TO CHANGE DRUGS STRUCTURE TO BE :STRUCTURE TO BE :

* Decrease in fat solublelity* Decrease in fat solublelity* to break in ionized* to break in ionized* Decrease in protein plasm/ tissue * Decrease in protein plasm/ tissue bound. bound.

Biotransformation Biotransformation Drug to be in active Drug to be in activeMetabolite Aktive : Metabolite Aktive :

Prontosil (In vitro) Prontosil (In vitro) Sulfanilamid.Sulfanilamid.

Proguanil Proguanil Metabilite aktif. Metabilite aktif.

MECHANISME OF BIOTRANSFORMATIONDRUG

ABSORBTION

DISTRIBUSTION protein bound

reseptor bound

Excretion

BIOTRANSFORMATION

(metabolism)

FASE I FASE II

1. Oksidation cytochrom axidase 1. Sulfation Sulfonyl transferase

2. Reduction Declorinasi 2. Glucorhonidation G.transferase

3. HidrolysisEsterase, Amidase 3. Conjugation As.Glukoronat

4. Hydrasi Hidrolase 4. AcetYlation, Methylation

BM < 300 BM> 300 BM< 300

URINE

Filtration, Secretion

PHARMAKODYNAMICPHARMAKODYNAMICPupose : Pupose : To know drug effectTo know drug effect

To know drug InteractionTo know drug InteractionTo know spectrum drug respons To know spectrum drug respons

MECHANISM OF ACTION : MECHANISM OF ACTION : 1.1. Interaction with drug reseptor Interaction with drug reseptor to change to change

biochemical & Physiological process biochemical & Physiological process ( Neurotransmitter)( Neurotransmitter) Respons. Respons.

2.2. Physical-chemist Characteristic of drug Physical-chemist Characteristic of drug Drug Drug responsrespons

3.3. Chelating Agent Chelating Agent drug respons drug respons4.4. Drug incorporation with celluler structure Drug incorporation with celluler structure drug drug

responrespon

DRUGS INTERACTION DRUGS INTERACTION

SYNERGISM SYNERGISM ADITIVE & POTENTIATIVE ADITIVE & POTENTIATIVE ANTAGONISM :ANTAGONISM :

* A. Chemist : Heparin X Protamin* A. Chemist : Heparin X Protamin* A. Functional/Physiological ( NE X * A. Functional/Physiological ( NE X

Histamin)Histamin)* A. Selective * A. Selective Receptor – Drugs. Receptor – Drugs. A. Selective Competitive : In seem A. Selective Competitive : In seem

receptor.receptor.Riversible : ACH x AtropinRiversible : ACH x AtropinIrreversible : NE x PrazosinIrreversible : NE x Prazosin

A. Selective non-competitive A. Selective non-competitive Different Different receptor, receptor,

D-R bound can”t break in highly dose.D-R bound can”t break in highly dose. Papaverin x Histamin ( Papaverin x ACH)Papaverin x Histamin ( Papaverin x ACH)

DOSE : DOSE : measure / quantity of drug to give measure / quantity of drug to give for individual until a cross activity for individual until a cross activity threshold but can”t cross Toxicity threshold but can”t cross Toxicity threshold.threshold.

Margin Of safety = LD50 : ED50Margin Of safety = LD50 : ED50

INFLUANCE FACTOR OF DOSE :INFLUANCE FACTOR OF DOSE :1.1. BODY WEIGHT( BW)BODY WEIGHT( BW)2.2. OLDOLD3.3. RUSTRUST4.4. SeXSeX5.5. Time of administrationTime of administration6.6. Patological DisholderPatological Disholder7.7. Genetic factorGenetic factor8.8. ToleranceTolerance

DRUG TOXICITYDRUG TOXICITY

Wrong in drug administration : Tetracycline (I.V) Wrong in drug administration : Tetracycline (I.V) konvulsive. Penicilline (I.V.) konvulsive. Penicilline (I.V.) Presipitation. Presipitation.

To remain the drug effect ( Excessive dose/ Over To remain the drug effect ( Excessive dose/ Over dose, Ren & liver malfunction, genetic factor, dose, Ren & liver malfunction, genetic factor, drug interaction).drug interaction).

Hypersensitive reaction (Allergy) : Dermatitis, Hypersensitive reaction (Allergy) : Dermatitis, Asthma, Shyok anafilactic, damage in liver & ren, Asthma, Shyok anafilactic, damage in liver & ren, damage in bonemarrow.damage in bonemarrow.

Blood discrasia, as well as Leucopenia, aplastic Blood discrasia, as well as Leucopenia, aplastic anaemia, haemolytic anaemia, thrombositopenia.anaemia, haemolytic anaemia, thrombositopenia.

Toxicity in liver & renToxicity in liver & ren Teratogenic effect. Teratogenic effect.

RESEARCH OF DRUGRESEARCH OF DRUG

1.1. TO INVENTION THE NEW DRUG TO INVENTION THE NEW DRUG * EMPERICALLY* EMPERICALLY* RASIONALITY* RASIONALITY* UNEXPECTED (KEBETULAN)* UNEXPECTED (KEBETULAN)* SCREENING PROCESS* SCREENING PROCESS

2. 2. PREKLINIK TRIAL PREKLINIK TRIAL * Activity Test & Side effect Test* Activity Test & Side effect Test* Uji Pharmacokinetic dan Pharmacodynamic* Uji Pharmacokinetic dan Pharmacodynamic* Uji Farmacy yang meliputi : * Uji Farmacy yang meliputi :

* Uji Kualitative dan Kuantitative bahan* Uji Kualitative dan Kuantitative bahan* Uji Stability* Uji Stability* Uji Sifat Physic dan Chemist* Uji Sifat Physic dan Chemist* Uji drug formulation* Uji drug formulation

* Uji general toxicity : Uji Acute , Sub Acute & Chronic * Uji general toxicity : Uji Acute , Sub Acute & Chronic Toxicity Test Toxicity Test

* Uji specific toxicity : Uji Teratogenic, Mutagenic dan * Uji specific toxicity : Uji Teratogenic, Mutagenic dan Carcinogenic Carcinogenic

3. 3. KLINICAL TRIAL KLINICAL TRIAL Devide 4 fase dan Uji Monitoring drug side effect (MESO).Devide 4 fase dan Uji Monitoring drug side effect (MESO).